The Gregory Fleming James Cystic Fibrosis Center at the University of Alabama at Birmingham was founded in 1981 in order to develop a multi- disciplinary program in CF basic research and therapy, and to draw upon talents of faculty residing in existing academic departments. The CF Center at UAB was the first to receive Research Development Program (RDP) support from the North American CF Foundation. With Dr. Sorscher's appointment as CF Center Director in April, 1994, the University of Alabama at Birmingham was reaffirmed its commitment to CF research. Using University funds as well as funds obtained from the State of Alabama, our Center has been provided with $2.1 million institutional operating costs from 1994 to 1999, followed by an ongoing budget provided by the university of $300,000 per year, to begin in 1999. In addition, approximately 12,000 sq. Ft. of laboratory space on the 7th floor of the Basic Health Sciences Building has been committed to be used specifically by the Cystic Fibrosis Research Center for CF research, including recruitment of new faculty dedicated to studies of basic science in CF. The traditional emphasis upon cystic fibrosis cell biology and electrophysiology remains an important strength of our CF Research Center, with many senior faculty engaged in studies of this type. Investigators have made many original observations concerning CFTR and CF pathogenesis. This overall SCOR proposal is directed towards a range of scientific observations intended to 1) improve the understanding of the role of CFTR in epithelial cell biology and 2) use basic characterization of CFTR to develop new ways to correct defects in CFTR function. The four projects include Project number 1: D.M. Bedwell, Ph.D., "Aminoglycoside Suppression of Premature Stop Mutations in CFTR", Project number 2: K.L. Kirk, Ph.D., "Structural Determinants of CFTR-Syntaxin Interactions", Project number 3: D.J. Benos, Ph.D., "Alternate C1- Secretory Pathways in Cystic Fibrosis", and Project number 4: E.J. Sorscher, M.D., "Biochemical Studies of the Cystic Fibrosis Gene Product". Support for three core facilities is also requested. These include Core A: D.M. Bedwell, Ph.D., "CF Animal Core", and Core C: E.J. Sorscher, M.D., "Administrative Core". The SCOR organizes the efforts of four established investigators towards the common goal of new and better understanding of important and clinically relevant aspects of CFTR cell biology.